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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1999-11-24
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pubmed:abstractText |
Transforming growth factor-beta1 (TGF-beta1) has been shown to induce apoptosis in normal or transformed hepatocytes. To elucidate the biochemical pathways leading to apoptosis induced by TGF-beta1 in human hepatoma cells (HuH-7), we examined the expression of Bcl-2-related proteins and X-chromosome-linked inhibitor of apoptosis (XIAP), and activation of the caspase cascade following TGF-beta1 treatment. Bcl-xL expression began to decline at 12 hours after TGF-beta1 treatment and progressively decreased to very low levels in a time-dependent manner. Bax expression showed a little change throughout the experiment. On the other hand, activation of caspase-8 was clearly observed at 36 hours after TGF-beta1 treatment, followed by activation of caspase-9, and caspase-3 was activated at 48 hours after treatment at which time apoptosis of HuH-7 cells was observed. TGF-beta1 significantly decreased XIAP expression in HuH-7 cells. Addition of an inhibitor of caspase-8 or caspase-3 (IETD-FMK or DEVD-CHO) markedly inhibited TGF-beta1-induced apoptosis of HuH-7 cells. Fas/Fas ligand (FasL) interactions in HuH-7 cells were not involved in the apoptotic process. Furthermore, epidermal growth factor (EGF) also completely inhibited TGF-beta1-induced apoptosis of HuH-7 cells by inhibiting activation of the caspase cascade. Our results suggested that activation of caspase-3 initiated through caspase-8 activation is involved in the apoptotic process induced by TGF-beta1 in HuH-7 cells. Our results also showed that down-regulation of the expression of Bcl-xL and XIAP by TGF-beta1 may facilitate activation of caspase-3 in these cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/aspartyl-glutamyl-valyl-aspartal,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0270-9139
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1215-22
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10534343-Antigens, CD95,
pubmed-meshheading:10534343-Apoptosis,
pubmed-meshheading:10534343-Carcinoma, Hepatocellular,
pubmed-meshheading:10534343-Caspase 3,
pubmed-meshheading:10534343-Caspase 8,
pubmed-meshheading:10534343-Caspase 9,
pubmed-meshheading:10534343-Caspases,
pubmed-meshheading:10534343-Cell Division,
pubmed-meshheading:10534343-Cysteine Proteinase Inhibitors,
pubmed-meshheading:10534343-Enzyme Activation,
pubmed-meshheading:10534343-Epidermal Growth Factor,
pubmed-meshheading:10534343-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:10534343-Humans,
pubmed-meshheading:10534343-In Situ Nick-End Labeling,
pubmed-meshheading:10534343-Kinetics,
pubmed-meshheading:10534343-Liver Neoplasms,
pubmed-meshheading:10534343-Oligopeptides,
pubmed-meshheading:10534343-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10534343-Time Factors,
pubmed-meshheading:10534343-Transforming Growth Factor beta,
pubmed-meshheading:10534343-Tumor Cells, Cultured,
pubmed-meshheading:10534343-bcl-X Protein
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pubmed:year |
1999
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pubmed:articleTitle |
Activation of caspase-8 in transforming growth factor-beta-induced apoptosis of human hepatoma cells.
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pubmed:affiliation |
Department of Clinical Pharmacology, Nagasaki University School of Medicine, Nagasaki, Japan.
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pubmed:publicationType |
Journal Article
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